The first topic involves experiments aimed at elucidating the role of regulatory and in particular suppressor cells in the lack of a primary cytotoxic T cell response to non-H-2 alloantigens. The Ia phenotype expressed on these cells will be investigated. The second series of experiments is designed to elucidate the nature of the cells involved in the activation and regulation of cytotoxic cells generated against syngeneic tumor cells by in vitro allostimulation. The third topic consists of experiments in which a number of protocols will be attempted in order to generate cytotoxic T cells with specificity for various differentiation and non-H-2 alloantigens expressed on natural killer and naturally cytotoxic cells. These cells will hopefully provide useful negative selection tools and may also serve to further elucidate the antigenic complexity of these non-H-2 antigens as have cytotoxic cells specific for determinants coded for by the H-2 gene complex.